CheckMate-026 Fails in Phase 3 - Nivolumab Monotherapy Does Not Improve PFS in NSCLC

August 5, 2016

Nivolumab failed to perform better than chemotherapy in patients with squamous as well as non-squamous non-small cell lung cancer (NSCLC).

Bristol Myer Squibb (BMS)’s recent immunotherapy success, nivolumab (Opdivo), failed to improve progression-free survival (PFS) when given alone to treatment-naïve patients with non-small cell lung cancer (NSCLC) whose tumors expressed at least 5% of the biomarker programmed death-ligand 1 (PD-L1).

The trial was designed to evaluate the programmed death-1 (PD-1) inhibitor nivolumab as monotherapy against investigator’s choice of chemotherapy in patients with NSCLC. The trial enrolled 541 treatment-naïve patients whose tumors expressed PD-L1; patients were randomized to receive either a 3 mg/kg intravenous infusion of nivolumab, every 2 weeks or the physician’s choice of a chemotherapy agent. For patients with squamous NSCLC, the comparator treatment was one of the following:

  • Gemcitabine with cisplatin
  • Gemcitabine with carboplatin
  • Paclitaxel with carboplatin

In patients with non-squamous NSCLC, the comparator treatment was one of the following:

  • Pemetrexed with cisplatin
  • Pemetrexed with carboplatin

The trial endpoint was disease progression, unacceptable toxicity, or completion of 6 cycles of treatment. The primary endpoint was PFS.

Despite these disappointing results, chief executive officer Giovanni Caforio, MD, is hopeful about the other combination treatment trials that BMS is pursuing simultaneously.

“Opdivo has become a foundational treatment that is transforming cancer care across multiple tumor types. While we are disappointed CheckMate -026 did not meet its primary endpoint in this broad patient population, we remain committed to improving patient outcomes through our comprehensive development program, including the ongoing Phase 3 CheckMate-227 study exploring the potential of the combination of Opdivo plus Yervoy for PD-L1 positive patients, and Opdivo plus Yervoy, or Opdivo plus chemotherapy in PD-L1 negative patients,” Caforio said in a press release.

BMS stock fell 16% following the news early Friday, while the price of its competitor, Merck, rose nearly 7%, according to Bloomberg. Merck manufacturer’s the other PD-1 inhibitor pembrolizumab (Keytruda).